2025
Structural basis for human NKCC1 inhibition by loop diuretic drugs
Zhao Y, Vidossich P, Forbush B, Ma J, Rinehart J, De Vivo M, Cao E. Structural basis for human NKCC1 inhibition by loop diuretic drugs. The EMBO Journal 2025, 44: 1540-1562. PMID: 39875725, PMCID: PMC11876703, DOI: 10.1038/s44318-025-00368-6.Peer-Reviewed Original ResearchConceptsLoop diureticsNa+-K+-Cl- cotransporterRenal salt reabsorptionEpithelial ion transportTreatment of edemaNKCC1 activityNKCC1 inhibitionChloride secretionSalt reabsorptionNKCC1Loop diuretic drugWNK kinasesDiuretic drugsBumetanideFurosemideHypertonic stressDiureticsIon transportTorsemideMolecular mechanismsCarboxyl groupsInhibitionCo-structureIons exitCells
2021
Dissection of Barrier Dysfunction in Organoid-Derived Human Intestinal Epithelia Induced by Giardia duodenalis
Holthaus D, Kraft M, Krug S, Wolf S, Müller A, Delgado Betancourt E, Schorr M, Holland G, Knauf F, Schulzke J, Aebischer T, Klotz C. Dissection of Barrier Dysfunction in Organoid-Derived Human Intestinal Epithelia Induced by Giardia duodenalis. Gastroenterology 2021, 162: 844-858. PMID: 34822802, DOI: 10.1053/j.gastro.2021.11.022.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisCaco-2 CellsChloridesCyclic AMPCyclic AMP-Dependent Protein KinasesCystic Fibrosis Transmembrane Conductance RegulatorDuodenumElectric ImpedanceGiardia lambliaGiardiasisHumansInterleukin-1Intestinal MucosaIon TransportNF-kappa BOrganoidsParasite LoadSignal TransductionSolute Carrier Family 12, Member 2Tight JunctionsTranscriptomeTumor Necrosis Factor-alphaConceptsG. duodenalis infectionBarrier dysfunctionGiardia duodenalisHuman duodenal tissueIntestinal barrier dysfunctionHuman intestinal epitheliumResponse element-binding proteinTight junction compositionProtozoan Giardia duodenalisAdequate cellular modelsChronic casesMajor expression changesPathophysiological mechanismsBarrier breakdownDuodenal mucosaGastrointestinal illnessDuodenal tissueBarrier lossPathogenic eventsHuman organoid systemEpithelial barrierTranswell systemChloride secretionIntestinal epitheliumTight junction componentsIntestinal TMEM16A control luminal chloride secretion in a NHERF1 dependent manner
Saha T, Aoun J, Hayashi M, Ali I, Sarkar P, Bag PK, Leblanc N, Ameen N, Woodward OM, Hoque KM. Intestinal TMEM16A control luminal chloride secretion in a NHERF1 dependent manner. Biochemistry And Biophysics Reports 2021, 25: 100912. PMID: 33537462, PMCID: PMC7838733, DOI: 10.1016/j.bbrep.2021.100912.Peer-Reviewed Original Research
2020
Purinergic Regulation of Bile Ductular Secretion
Dranoff J. Purinergic Regulation of Bile Ductular Secretion. 2020, 96-104. DOI: 10.1201/9780367813888-9.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsP2Y receptorsPurinergic receptorsIntestinal epitheliumExtracellular nucleotidesP2Y receptor subtypesP2 receptorsReceptor subtypesRespiratory epitheliumP1 receptorsMucin secretionNucleotide receptorsPurinergic agonistsPlatelet aggregationPurinergic regulationChloride secretionDistinct receptorsDuctular secretionNucleoside receptorsEpithelial secretionEpitheliumReceptorsSalivary glandsSecretionSecretory epitheliumRenal epithelium
2013
Activation of AMPK Inhibits Cholera Toxin Stimulated Chloride Secretion in Human and Murine Intestine
Rogers AC, Huetter L, Hoekstra N, Collins D, Collaco A, Baird AW, Winter DC, Ameen N, Geibel JP, Kopic S. Activation of AMPK Inhibits Cholera Toxin Stimulated Chloride Secretion in Human and Murine Intestine. PLOS ONE 2013, 8: e69050. PMID: 23935921, PMCID: PMC3728293, DOI: 10.1371/journal.pone.0069050.Peer-Reviewed Original ResearchConceptsIntestinal chloride secretionCholera toxinChloride secretionPharmacological activationFluid accumulationColonic cryptsSupplemental treatment strategyAcute diarrheal illnessChloride effluxCystic fibrosis transmembrane conductance regulatorExcised intestinal segmentsRat colonic cryptsMurine colonic mucosaMucosal sheetsDiarrheal illnessIntestinal loopsEnterotoxigenic diarrheaColonic mucosaTreatment strategiesIntestinal segmentsUssing chambersAMPK activator AICARMurine intestineTissue levelsMetformin
2011
Hypoxia Inhibits Colonic Ion Transport via Activation of AMP Kinase
Collins D, Kopic S, Bachlechner J, Ritter M, Winter DC, Geibel JP. Hypoxia Inhibits Colonic Ion Transport via Activation of AMP Kinase. Annals Of Surgery 2011, 254: 957-963. PMID: 21562404, DOI: 10.1097/sla.0b013e31821d477f.Peer-Reviewed Original ResearchConceptsCystic fibrosis transmembrane conductance regulatorChloride secretionMucosal hypoxiaAcute hypoxiaColonic electrolyte transportColonic mucosal functionIschemic intestinal injuryElectrogenic chloride secretionColonic ion transportPotential therapeutic targetHuman colonic mucosaIntracellular chloride concentrationRat colonic cryptsEpithelial ion transportFibrosis transmembrane conductance regulatorIschemic colitisIntestinal injuryColonic obstructionInhibition of CFTRMucosal functionAnastomotic failureAcute effectsColonic mucosaAdaptive cellular responseTransmembrane conductance regulatorThe flavonone naringenin inhibits chloride secretion in isolated colonic epithelia
Collins D, Kopic S, Geibel JP, Hogan AM, Medani M, Baird AW, Winter DC. The flavonone naringenin inhibits chloride secretion in isolated colonic epithelia. European Journal Of Pharmacology 2011, 668: 271-277. PMID: 21762688, DOI: 10.1016/j.ejphar.2011.06.052.Peer-Reviewed Original ResearchConceptsHuman colonic mucosaChloride secretionAntisecretory actionColonic mucosaCo-transporter inhibitorsEffect of naringeninIntracellular cAMP generationColonic cell lineAntisecretory effectColonic functionColorectal cancerProtective effectUssing chambersColonic epitheliumSecretory functionCAMP generationInhibitory actionBasolateral NKCC1Human colonRatsSecretionIntracellular acidificationConflicting resultsCell linesMucosa
2010
Evidence for intestinal chloride secretion
Murek M, Kopic S, Geibel J. Evidence for intestinal chloride secretion. Quarterly Journal Of Experimental Physiology And Cognate Medical Sciences 2010, 95: 471-478. PMID: 20233891, DOI: 10.1113/expphysiol.2009.049445.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChloride ChannelsChloridesCLC-2 Chloride ChannelsCystic Fibrosis Transmembrane Conductance RegulatorDiarrheaEnterocytesHumansIntestinal AbsorptionIntestinal MucosaIntestinal SecretionsPotassium ChannelsSodium-Potassium-Chloride SymportersSodium-Potassium-Exchanging ATPaseTight JunctionsWater-Electrolyte Balance
2009
The Vibrio cholerae Cytolysin Promotes Chloride Secretion from Intact Human Intestinal Mucosa
Debellis L, Diana A, Arcidiacono D, Fiorotto R, Portincasa P, Altomare DF, Spirlì C, de Bernard M. The Vibrio cholerae Cytolysin Promotes Chloride Secretion from Intact Human Intestinal Mucosa. PLOS ONE 2009, 4: e5074. PMID: 19333391, PMCID: PMC2659442, DOI: 10.1371/journal.pone.0005074.Peer-Reviewed Original ResearchConceptsToxin-coregulated pilusPathogenesis of VibrioCholera toxinSigmoid colon specimensV. cholerae O1 El Tor strainsHuman intestinal mucosaO1 El Tor strainsVibrio choleraeInflammatory enterocolitisSubtotal colectomyWatery diarrheaBasal valuesIntestinal mucosaElectrophysiological parametersNon-toxigenic strainsUssing chambersColon specimensHealthy colon tissueDiarrheaChloride secretionEl Tor strainsColon tissuesSporadic outbreaksParacellular permeabilityClinical samples
2006
Assessment of cystic fibrosis transmembrane conductance regulator (CFTR) activity in CFTR-null mice after bone marrow transplantation
Bruscia EM, Price JE, Cheng EC, Weiner S, Caputo C, Ferreira EC, Egan ME, Krause DS. Assessment of cystic fibrosis transmembrane conductance regulator (CFTR) activity in CFTR-null mice after bone marrow transplantation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 2965-2970. PMID: 16481627, PMCID: PMC1413802, DOI: 10.1073/pnas.0510758103.Peer-Reviewed Original ResearchConceptsCftr-/- miceEpithelial cellsNasal epitheliumBM-derived cellsBone marrow transplantationWild-type BMAirway epithelial cellsCystic fibrosis transmembrane conductance regulator (CFTR) activityCystic fibrosis miceRare epithelial cellsCftr-null miceMarrow transplantationBM transplantationFibrosis miceRespiratory tractCFTR activityGI tractBone marrowGastrointestinalChloride secretionCFTR-dependent chloride secretionIndividual miceTransplantationDifferent dosesMice
1996
Na:K:2Cl Cotransporter (NKCC) of Intestinal Epithelial Cells SURFACE EXPRESSION IN RESPONSE TO cAMP*
D'Andrea L, Lytle C, Matthews J, Hofman P, Forbush B, Madara J. Na:K:2Cl Cotransporter (NKCC) of Intestinal Epithelial Cells SURFACE EXPRESSION IN RESPONSE TO cAMP*. Journal Of Biological Chemistry 1996, 271: 28969-28976. PMID: 8910547, DOI: 10.1074/jbc.271.46.28969.Peer-Reviewed Original ResearchConceptsChloride secretionSurface expressionBumetanide-sensitive NaMonoclonal antibodiesIntestinal chloride secretionIncreased surface expressionCell surface expressionEpithelial cell lineNKCC activityT84 monolayersCotransport activityAgonist stimulationCAMP agonistsEpithelial uptakeCotransporterBasolateral domainIntestinal epitheliaSurface biotinylationNKCCConfocal localizationApproximately 6-foldCell linesF-actin cytoskeletonSecretionImmunoelectron microscopy
1995
Distribution and diversity of Na-K-Cl cotransport proteins: a study with monoclonal antibodies
Lytle C, Xu J, Biemesderfer D, Forbush B. Distribution and diversity of Na-K-Cl cotransport proteins: a study with monoclonal antibodies. American Journal Of Physiology 1995, 269: c1496-c1505. PMID: 8572179, DOI: 10.1152/ajpcell.1995.269.6.c1496.Peer-Reviewed Original ResearchConceptsNa-K-Cl cotransporterNa-K-Cl cotransport proteinNa-K-ClMonoclonal antibodiesEpithelial salt transportCell volume homeostasisT antibodyAscending limb cellsImmunoreactive proteinBinding site densityChloride reabsorptionChloride secretionBasolateral marginsParotid glandCotransporter proteinApical membraneWestern blot analysisVolume homeostasisAcinar cellsWestern blot analysis of membranesCotransporterImmunocytochemical studiesRabbit kidneyAmount of immunoreactive proteinRabbit parotid gland
1992
cGMP-dependent protein kinase regulation of a chloride channel in T84 cells
Lin M, Nairn A, Guggino S. cGMP-dependent protein kinase regulation of a chloride channel in T84 cells. American Journal Of Physiology 1992, 262: c1304-c1312. PMID: 1317106, DOI: 10.1152/ajpcell.1992.262.5.c1304.Peer-Reviewed Original ResearchConceptsProtein kinaseChloride channelsIntestinal epithelial cellsCGMP-dependent protein kinaseProtein kinase regulationApical membraneDependent protein kinaseT84 cellsEpithelial cellsInhibitor of PKGKinase regulationCatalytic subunitCombination of ATPNonhydrolyzable formExcessive fluid secretionIntracellular faceEscherichia coliElevated guanosineSingle-channel recordingsATPKinasePKGLinear current-voltage relationshipCellsChloride secretion
1989
Regulation of Chloride Channels by Protein Kinase C in Normal and Cystic Fibrosis Airway Epithelia
Li M, McCann J, Anderson M, Clancy J, Liedtke C, Nairn A, Greengard P, Welsch M. Regulation of Chloride Channels by Protein Kinase C in Normal and Cystic Fibrosis Airway Epithelia. Science 1989, 244: 1353-1356. PMID: 2472006, DOI: 10.1126/science.2472006.Peer-Reviewed Original ResearchConceptsProtein kinase CChloride channelsKinase CApical membrane chloride channelMembrane chloride channelCystic fibrosis cellsMembrane proteinsCell-free membraneCystic fibrosis airway epitheliaChloride secretionIntact cellsPhorbol esterPhysiological statusDefective regulationAirway epithelial cellsEpithelial cellsCellsRegulationChannel inactivationCystic fibrosisActivationCalcium concentrationLow calcium concentrationsProteinAirway epithelium
1988
Cyclic AMP-dependent protein kinase opens chloride channels in normal but not cystic fibrosis airway epithelium
Li M, McCann J, Liedtket C, Nairn A, Greengard P, Welsh M. Cyclic AMP-dependent protein kinase opens chloride channels in normal but not cystic fibrosis airway epithelium. Nature 1988, 331: 358-360. PMID: 2448645, DOI: 10.1038/331358a0.Peer-Reviewed Original ResearchConceptsCAMP-dependent protein kinaseProtein kinaseRegulatory proteinsCl- channelsCyclic AMP-dependent protein kinaseAMP-dependent protein kinaseCommon lethal genetic diseaseNormal cellsLethal genetic diseaseApical Cl- channelsCatalytic subunitCell-free patchesCystic fibrosis airway epitheliaGenetic diseasesVariety of hormonesCF airway epitheliaCF cellsChloride channelsKinaseIntracellular levelsProteinAirway epitheliumCyclic AMPChloride secretionCells
1984
Pardaxin increases solute permeability of gills and rectal gland in the dogfish shark (Squalus acanthias)
Primor N, Zadunaisky J, Murdaugh H, Boyer J, Forrest J. Pardaxin increases solute permeability of gills and rectal gland in the dogfish shark (Squalus acanthias). Comparative Biochemistry And Physiology Part C Toxicology & Pharmacology 1984, 78: 483-490. PMID: 6149101, DOI: 10.1016/0742-8413(84)90119-1.Peer-Reviewed Original Research
1983
Role of calcium in the regulation of colonic secretion in the rat
Zimmerman T, Dobbins J, Binder H. Role of calcium in the regulation of colonic secretion in the rat. American Journal Of Physiology 1983, 244: g552-g560. PMID: 6133455, DOI: 10.1152/ajpgi.1983.244.5.g552.Peer-Reviewed Original ResearchConceptsSerosal calciumRole of calciumExtracellular calciumElectrolyte transportNeutral sodium chloride absorptionEffect of bethanecholEffect of theophyllineMuscarinic cholinergic agonistNet sodium absorptionSodium chloride absorptionNet chloride absorptionCalcium-free mediumNeutral NaCl absorptionColonic secretionCholinergic agonistsIntracellular calciumBethanecholNet sodiumRat colonChloride secretionJNanetSodium absorptionChloride absorptionJClnetNaCl absorption
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